PB2223: CLINICOPATHOLOGICAL, CYTOGENETIC AND MOLECULAR CHARACTERISTICS OF PATIENTS WITH NON-CML MYELOPROLIFERATIVE NEOPLASMS: A SINGLE CENTER STUDY
Authors: Vinay Anand Guntiboina, Arijit Nag, Jeevan Kumar, Sushant Sonu Vinarkar, Ashish Rath, Saurabh Bhave, Vivek Radhakrishnan, Deepak Kumar Mishra, Reena Nair, Mammen Chandy
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Classical myeloproliferative neoplasms (MPNs) are a rare group of clonal disorders affecting cells of the myeloid lineage which includes essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). There is a paucity of data on classical MPNs, excluding Chronic Myeloid Leukemia (CML) from India, partly due to lack of widespread molecular testing and limited resources. Therefore, we conducted a data analysis of all non-CML MPN patients presenting to our center in Eastern India. Aims: This is a study of the clinicopathological characteristics of classical MPNs presenting at our centre over a time period of 10 years. The primary objective was to determine the clinicopathological distribution of this cohort of patients with a secondary objectives of analysing the cytogenetic and molecular data as well as response at 48 weeks to individual disease related therapy and survival analysis. Methods: This is an observational, single center study of all patients with a diagnosis of a non-CML MPN registered in Tata Medical Center, Kolkata between May 2011 to December 2022. Data collection was done through review of electronic medical records (EMR). Patients who refused to consent, did not meet the current diagnostic criteria or had only a single clinic visit were excluded from the analysis. Objective response rate was defined as the proportion of patients who had more than a partial response as per the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT). Descriptive statistics and survival analysis was done using SPSS v26.0. Results: Of the 105 evaluable patients, 31 were diagnosed with PV, 30 with ET and 43 had PMF. Patients had a male preponderance (2.1:1) and a median age of 51 years (range: 2-83 years). Patients were most commonly diagnosed incidentally (33.3%), except in the PMF cohort wherein patients presented with fatigue (51.2%). Amongst patients with PMF (n=43), 9 had a hypocellular marrow compared to 28 with a hypercellular marrow, reflecting the possibility of pre fibrotic MF. Cytogenetic studies were carried out in 45 patients (n=45, 42.9%) with a majority of patients displaying a normal karyotype (82.2%). Mutational profile most commonly revealed the presence of JAK2 V617F (n=55, 52%) followed by mutations in Calreticulin (CALR) seen in 12 patients (11%) and MPL in 5% patients. Additional analysis through next generation sequencing (n=20) revealed the presence of ASXL1 mutations (2.9%), TET2 and U2AF1 (0.9% each). Patients with PV and ET were most commonly treated with hydroxyurea (90.3% and 100%, respectively), while it was given in 37.2% of patients with PMF. Four patients (9.3%) with PMF underwent allogeneic hematopoietic cell transplantation. The objective response rate at 48 weeks was 48.4%, 83.3% and 41.9% in PV, ET and PMF, respectively. Median progression free survival was 188 months and 173 months in PV and PMF but was not reached in ET while the median overall survival was not reached in the PV and ET cohorts and was 177 months in patients with PMF (log rank test, p=0.013). Summary/Conclusion: This is the second largest data set highlighting the clinicopathological characteristics of classical MPNs, excluding CML, from India. The molecular profile of this cohort is consistent with existing literature and also highlights the presence of additional mutations through the routine incorporation of NGS in the diagnostic work up. The availability of such data will aid in the application of novel prognostication tools in the management of these neoplasms.Keywords: Myeloproliferative disorder, Myelofibrosis, Molecular markers, Polycythemia vera